Recurrent ganglioneuroma in PTPN11 ‐associated Noonan syndrome: A case report and literature review

Abstract Noonan syndrome (NS) is an autosomal dominant condition with variable expressivity most commonly due to a germline pathogenic variant in PTPN11 , which encodes the protein tyrosine phosphatase SHP‐2. Gain‐of‐function variants in PTPN11 are known to promote oncogenic behavior in affected tissues. We report the clinical description of a young adult male presenting with relapsing ganglioneuromas, dysmorphic features, cardiac abnormalities, and multiple lentigines, strongly suspicious for NS. Solid tumor testing identified the recurrent pathogenic c.922G>A (p.Asn308Asp) in PTPN11 . Proband and parental blood sampling testing confirmed c.922G>A as a de novo germline alteration. Comprehensive literature review of solid tumors specifically associated to PTPN11 , indicates that this is the first documentation of ganglioneuroma and its clinical recurrence after resection in conjunction with a genetically confirmed NS diagnosis. The findings in our patient further extend the list of neuroblastic and neural crest‐derived neoplasms associated with this condition.